Circulating TMAO levels would increase with age, and be associated with AD-like behavioral and pathological profile of APP/PS1 mice.TMAO reduction by DMB could reverse the upregulation of clusterin levels in the plasma, Aβ1–42, β-secretase, βCTF, and proinflammatory cytokines in the hippocampus, and cognition deficiencies in AD model mice. This evidence concerns the gene APP and Alzheimer disease.